GELATINE TANNATE IN THE

MANAGEMENT OF ACUTE
GASTROENTERITIS IN CHILDREN: A
RANDOMISED CONTROLLED TRIAL
ABSTRACT
OBJECTIVE, DESIGN, SETTING
 Objective To assess the efficacy of gelatine tannate (a
complex of tannic acid with astringent and
antiinflammatory properties, and a protective gelatine)
for the treatment of acute gastroenteritis (AGE) in
children.
 Design Randomised, double-blind, placebo-controlled
trial. Intention-to-treat analysis.
 Setting Two paediatric hospitals in Warsaw.
PARTICIPANTS
 Children younger than 5 years of age with AGE, defined
as a change in stool consistency to a loose or liquid form
(according to the Bristol Stool Form Scale or Amsterdam
Stool Form Scale) and/or an increase in the frequency of
evacuations (≥3 in 24 hours), lasting for no longer than 5
days.
INTERVENTIONS
 Seventy-two children were assigned to receive gelatine
tannate (n=36) or placebo (n=36) in addition to standard
rehydration therapy. The gelatine tannate was
administered at an age-dependent dose (250–500 mg),
and both study products were taken four times per day
for 5 days.
PRIMARY AND SECONDARY OUTCOME
MEASURES
 The main outcome measure was duration of diarrhoea.
Secondary outcomes included the need for intravenous
rehydration, need for hospitalisation of outpatients,
number of watery stools per day, vomiting, weight gain,
adverse events, recurrence of diarrhoea, severity of
diarrhoea according to the Vesikari Scale and use of
concomitant medications
RESULTS
 Sixty-four children (89%) completed the intervention
and were included in the analysis. The duration of
diarrhoea after randomisation was similar in the gelatine
tannate and placebo groups (75.6±27.8 vs 75.5±29.0
hours, respectively, mean difference 0.1 hours, 95% CI
−14.1 to 14.3 hours). There was no significant difference
between groups in the number of watery stools per day
throughout the study period. There were also no
differences in any other secondary outcome measures
between groups.
CONCLUSION
 In children with AGE younger than 5 years of age,
gelatine tannate was ineffective as an adjunct to
rehydration therapy
INTRODUCTION
 The main objectives in the management of acute
gastroenteritis are the prevention or treatment of
dehydration, promotion of weight gain following
rehydration and reduction of the duration of diarrhoea
and quantity of stool output.
 The key treatment is oral rehydration with a hypo-
osmolar solution.
 Recently, in many countries, gelatine tannate is being
marketed for the treatment of acute gastroenteritis.
 Gelatine tannate consists of tannic acid suspended in a
gelatine solution.
 The specific mechanisms by which gelatine tannate may
act against gastrointestinal infections remain unknown.
 It is known, however, that it forms a biofilm, which
mechanically protects the gastrointestinal mucosa and
causes precipitation of proinflammatory proteins such as
mucoproteins in the intestinal mucosa.
 In addition, it inhibits the growth of bacteria such as
Bacteroides fragilis, Clostridium perfringens,
Escherichia coli, Enterobacter cloacae, Salmonella
typhimurium, Helicobacter pylori, Listeria
monocytogenes and in vitro mycobacterial Vibrio
cholerae.
 The anti-inflammatory action of gelatine tannate also
involves blocking inflammatory agents in the
gastrointestinal mucosa.
 There is no evidence to support the use of gelatine
tannate for treating acute gastroenteritis in children (ie,
no randomised controlled trials; important outcomes not
addressed) and only scant evidence to support the use of
gelatine tannate in adults.
 Thus, our aim was to assess the efficacy of gelatine
tannate for the management of acute gastroenteritis in
children.
METHODS
TRIAL DESIGN
 This was a randomised, double-blind, placebo-controlled
trial, conducted in two paediatric hospitals in Warsaw,
Poland.
 Parents or legal guardians were fully informed about the
aims of the study, and informed written consent was
obtained from them.
PARTICIPANTS
 Eligible participants were children younger than 5 years
with acute gastroenteritis, defined as a change in stool
consistency to a loose or liquid form (according to the
Bristol Stool Form (BSF) Scale, or, in the case of infants,
the Amsterdam Stool Form (ASF) Scale) and/or an
increase in the frequency of evacuations (typically ≥3 in
24 hours), lasting for no longer that 5 days.
PARTICIPANTS
 Exclusion criteria included the use of antibiotics,
gelatine tannate, diosmectite, probiotics, racecadotril or
zinc (including zinc-containing oral rehydration
solution) within a week prior to enrolment; exclusive
breast feeding; chronic diarrheal gastrointestinal;
immunodeficiencies and malnutrition
(weight/height/length under third percentile, WHO Child
Growth Standards were used).
INTERVENTION
 Participants were randomly assigned to receive gelatine
tannate or a comparable placebo (maltodextrin) in
addition to standard rehydration therapy.
 The dose of the active product or placebo was age
dependent (ie, in children younger than 3 years of age,
the dose was 250 mg, and, in children older than 3 years
of age, the dose was 500 mg).
INTERVENTION
 Both the gelatine tannate and placebo were taken orally,
four times per day, for 5 days.
 All study participants were followed up for the duration
of the intervention (5 days), and then for an additional 48
hours.
 Compliance was assessed by counting the number of
sachets of study products left unused.
 We assumed that participants receiving <75% of the
recommended doses were treated as non-compliant.
STUDY PROCEDURE
 For initial rehydration, all children were treated
according to 2014 European recommendations (fast oral
rehydration over 3–4 hours by mouth with a hypotonic
solution).
 Intravenous fluid therapy was administered during the
rehydration phase if there was failure to achieve
adequate rehydration within the first 3–4 hours or if
there were intensified signs of dehydration despite the
intake of the estimated fluid requirements.
STUDY PROCEDURE
 After all of the signs of dehydration had disappeared,
ORS was given for ongoing losses until the diarrhoea
stopped.
 Rapid reintroduction of the previous diet after successful
rehydration was recommended. At all times, breast
feeding was allowed. Children were discharged from the
hospital once a stable clinical condition had been
achieved.
OUTCOME MEASURES
 The primary outcome measure was the duration of
diarrhoea, defined as the time until the normalisation of
stool consistency according to the BSF or ASF Scale (on
BSF Scale, numbers 2, 3, 4 and 5; on ASF scale, letters
B or C) or the time until the normalisation of the number
of stools (compared with the period before the onset of
diarrhoea) as well as the presence of normal stools for 48
hours.
OUTCOME MEASURES
 The secondary outcome measures included the need for
intravenous rehydration, need for hospitalisation of
outpatients, number of watery stools per day, vomiting,
weight gain, adverse events, recurrence of diarrhoea (48
hours after the intervention), severity of diarrhoea
according to the Vesikari Scale11 and use of concomitant
medications.
ALLOCATION CONCEALMENT AND
BLINDING
 A computer-generated randomization list prepared by a
person unrelated to the trial was used to allocate
participants to the study groups in blocks of eight.
 Consecutive randomisation numbers were given to
participants at enrolment.
 The study products were delivered to the physicians in
small envelopes labeled with the consecutive numbers
and doses.
ALLOCATION CONCEALMENT AND
BLINDING
 The physicians were blinded to the meaning of the
numbers, and the sealed envelopes were deposited in a
safe place in the administrative part of the department.
 Researchers, caregivers, outcome assessors and the
person responsible for the statistical analysis were
blinded to the intervention until the completion of the
study and the analysis of the data.
SAMPLE SIZE CALCULATION
 To detect such a difference in the duration of diarrhoea
between the study groups with a power of 90% and
α=0.01, we determined that a sample of 60 children was
needed.
 Assuming approximately 20% loss to follow-up, we
aimed to recruit a total of 72 children for this study.
STATISTICAL ANALYSIS
 The statistical analyses were conducted using StatsDirect
V.3.0.181 computer software.
 The Shapiro-Wilk W test was used to investigate a
sample for evidence of non-normality.
 Student’s t-test was used to compare means of
continuous variables approximating a normal
distribution.
 For non-normally distributed variables, the
MannWhitney U test was used.
STATISTICAL ANALYSIS
 The χ2 test or Fisher’s exact test was used, as
appropriate, to compare percentages.
 The same computer software was used to calculate the
risk ratio (RR) and mean or median difference (MD), as
appropriate, both with a 95% CI.
PATIENT INVOLVEMENT
 Patients were not involved in setting the study protocol
and implementation, and the dissemination of the result.
RESULT
RESULT
RESULT
RESULT
DISCUSSION
PRINCIPAL FINDINGS
 This randomised, double-blind, placebo-controlled study
showed that in children younger than 5 years with acute
gastroenteritis, administration of gelatine tannate
compared with placebo was ineffective as an adjunct to
oral rehydration therapy
Strengths

 This study was a randomised controlled trial

 We maintained blinding the selection, treatment, data management
and data analyses phases of the study
 Follow-up was adequate
 This study used the validated BSF Scale or the ASF Scale for
assessment of the consistency of stools depending on the age of the
participants.
 The sample size was predefined.

Limitations

 This study did not assess stool volume as the primary outcome
measure
CONCLUSIONS
CONCLUSIONS
 In summary, gelatine tannate, as dosed in this study,
administered as an adjunct to rehydration for the
management of acute gastroenteritis in children younger
than 5 years was not effective.